As COVID-19 variants have emerged, so have questions about the effectiveness of tests for infection. While the risk of mutations significantly limiting their ability to detect the novel coronavirus is thought to be relatively low, companies that make COVID-19 tests are moving quickly to enhance and revalidate their products.

“The primary challenge for COVID-19 diagnostics companies is ensuring their products continue to accurately test for the virus, regardless of the variant, and to innovate at the challenging pace required to remain clinically relevant,” Graham Mullis, CEO of Novacyt SA, told BioWorld.

That COVID-19 would evolve and mutate was always anticipated. What was unknown was the degree to which these mutations would impact the speed of the virus’ transmission or the efficacy of potential treatments. The evidence thus far suggests they are more contagious and may also be more lethal than the original strain first isolated in Wuhan, China, though more time and study is needed to ascertain their lethality.

Regardless, COVID-19 variants are here, and more are likely to emerge over time, increasing demand for COVID-19 tests capable of both diagnosing SARS-CoV-2 virus and differentiating between the different viral strains.

Challenges

According to the Foundation for Innovative New Diagnostics’ (FIND) SARS-CoV-2 diagnostic pipeline, there are 1,104 tests in development or with some level of regulatory authorization (not necessarily full approval). That includes 428 molecular tests and 638 immunoassays.

Sergio Carmona, CMO of FIND

“I would say we shouldn’t panic” if new variants are missed with the current commercially available products. “But understanding at an epidemiological level, a clinical level, what these new variants are doing is key,” Sergio Carmona, FIND’s CMO, told BioWorld. “You need to be setting up those systems to watch early on how this bio-evolution starts affecting clinical outcomes.”

According to Carmona, the value of knowing a person has the variant is more likely to be of benefit in decisions around which vaccines will be more effective for a particular country, rather than diagnosing.

“For routine diagnostics, what you need to know is do you have COVID or not? And for that … most manufacturers [of molecular tests] have learned from the past that you need multiple sites that serve to use as your targets for amplification,” he said. For the antigen rapid diagnostic tests (RDTs), the majority have both a capture and a detection antibody to a nucleocapsid protein, and most of the current variants of concern affect the spike protein.

“So, from what we know today, both the antigen RDTs and the majority of the molecular diagnostic tools are okay,” Carmona said.

Where a difference in performance comes into play is with the ability of molecular tests to predict the use of other signals, he added. With the U.K. variant, “it was a drop in the S signal, and there were one or two assays, for example, the Thermo Fisher one, that used this gene as one of the genes that you would amplify. And, inadvertently, it became a surrogate for detecting variants.”

If the goal is to detect variants, those tests would probably not be for routine diagnostics, but rather for researchers, developers and epidemiologists, and they would involve sequencing, Carmona said.

“There are some PCR-targeted solutions just to detect those mutations, but those would be mostly confined for research and monitoring emerging variants.”

Novacyt, T2 Biosystems

Novacyt, of Vélizy-Villacoublay, France, is one of the companies developing such assays. It recently launched a PCR genotyping assay portfolio to detect COVID-19 variants. Based on the analysis of single nucleotide polymorphisms (SNPs), the SNPsig portfolio is designed to run on central laboratory systems and on the company’s q16 and q32 rapid PCR systems as research-use-only (RUO) products. While the RUO designation means that people can access it immediately, the company is also looking for regulatory approval in key markets, which will allow the assays to reach the broadest number of people, Mullis said.

The first three SNPsig assays enable the identification of the original strain of the virus, the U.K. (B.1.1.7), South Africa (B.1.351) and Brazil (B.1.1.28) variants, as well as any new variant carrying the N501Y mutation.

Graham Mullis, CEO of Novacyt SA

“Our SNPsig assays are the same high level of accuracy as our PCR SARS-CoV-2 portfolio,” Mullis said. More variants will be added as they are identified.

Mullis attributes Novacyt’s quick response and dynamic innovation model to the company’s extensive surveillance program. “This has allowed us to keep track of new SARS-CoV-2 variants in real time as they arise and, as a result, continue to analyze our assays to ensure they remain able to detect the virus with the same high level of accuracy,” he said.

Novacyt began the surveillance program when there were just a few hundred reported SARS-CoV-2 sequences. That number has since grown to 308,000, and Novacyt continues to review them each week. The company is also working with a global network of virologists, tracking variants to identify mutations as they are reported and sequenced.

Also of note in the effort to remain relevant in the wake of COVID-19 variants is T2 Biosystems Inc. The Lexington, Mass.-based company said its T2SARS-CoV-2 panel, which runs on its fully automated T2dx instrument, can detect all three known variants.

“The majority of the mutations identified in these variants have been associated with the S gene, which encodes the spike protein,” Roger Smith, vice president of science, research and development at T2 Biosystems, told BioWorld. “The design of the T2SARS-CoV-2 panel focused on the detection of the N gene in SARS-CoV-2, which encodes the nucleocapsid and may be less prone to mutations.”

To ensure continued performance, the company is regularly monitoring the ability of the T2SARS-CoV-2 panel to detect COVID-19 infection, including any newly arising variants, he said. This includes actively performing alignment tests, using thousands of genome sequences available in the National Center for Biotechnology Information nucleotide database and GISAID database, to determine if the panel remains effective in detecting SARS-CoV-2.

Seegene, Innova Medical

The first company to roll out a COVID-19 diagnostic variant test was Seegene Inc. The Seoul-based company’s Allplex SARS-CoV-2 Variants I Assay detects and differentiates the wild virus and major genetic variations, including those originating in the U.K., South Africa, Brazil and Japan. It is also capable of prescreening suspicious new variants.

The test uses Seegene’s real-time PCR method of mTOCE, which allows the test to target a specific spot where mutation occurs, enabling precise detection and differentiation of COVID-19 and its mutated versions with a single tube of reagent.

The company said its priority was to supply its COVID-19 variant tests to global organizations and governments.

Innova Medical Group Inc., of Pasadena, Calif., also has reported that its SARS-CoV-2 Antigen Test kits can successfully detect the mutated U.K., South Africa and Brazil variants. Innova can produce more than 10 million of its rapid antigen tests per day, with plans to scale capacity to about 50 million by spring of 2021.